Thromboembolism and bleeding in newly diagnosed Multiple Myeloma – Rates, risk profile and patterns of thromboprophylaxis

Introduction Patients with multiple myeloma (MM) treated with immunomodulatory drugs (IMiDs) have a high risk of venous thromboembolisms (VTE). Guidelines suggest pharmacological thromboprophylaxis in all patients treated with IMiD-based regimens, using aspirin for patients at low, and low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) for those at high VTE risk. Direct oral anticoagulants (DOACs) have not yet been sufficiently studied in this indication but could be an effective and convenient alternative and have since 2012 been offered as such at our centre.

Method For this retrospective cohort study, we screened all patients that presented at our centre between January 2012 and January 2022 with MM or related plasma cell disorders. Inclusion criteria were newly diagnosed biopsy-proven MM within this time range and induction treatment at our centre. Data were collected through review of medical records. Baseline disease characteristics and risk factors for VTE according to the IMPEDE-VTE and SAVED scores were assessed at time of diagnosis. Anti-myeloma treatment, thromboprophylaxis and thrombotic as well as bleeding events were recorded during a two-year observational period. In those with multiple VTE or bleeding events, only the first event, respectively, was counted. For analysis of outcomes according to type of thromboprophylaxis, the antithrombotic drug prescribed prior to the event of interest was considered in an intention-to-treat manner [1] [2] [3] [4] [5].

Results Of 292 patients screened, 208 were included in the analysis based on predefined inclusion and exclusion criteria. Characteristics of patients are shown in [Fig. 2]. During the 2-year follow up, 19 (9.1%) patients developed VTE, 4 (1.9%) had arterial thromboembolism, 35 (16.8%) had bleeding events and 20 (9.6%) patients died ([Fig. 1]).

Fig. 1  Demographic and clinical characteristics of 208 patients diagnosed with MM between January

Fig. 2  2-Year Cumulative Incidence of VTE and bleeding stratified by type of thromboprophylaxis

A high IMPEDE-VTE score was associated with risk for VTE (HR for high (≥8 points) vs. low (≤3 points) IMPEDE-VTE: 3.994 [95%CI 1.072-14.881], p=0.039; HR increase per 1 point increase: 1.193 [95%CI 1.04-1.369], p=0.012). The SAVED score did not predict VTE in our cohort (HR for high vs. low SAVED: 1.006 [95%CI 0.354-2.855], p=0.992).

The type of thromboprophylaxis was significantly associated with both risk of VTE and risk of bleeding ([Fig. 2]). Seven out of 18 patients (38.9%) had a VTE while not on any type of thromboprophylaxis, 9 out of 65 (13.8%) while on aspirin, 2 out of 25 (8%) while on LMWH. None of the 90 patients on DOACs or the 3 patients on VKAs had a VTE. Bleeding occurred in 47.4% of patients without thromboprophylaxis, in 9.4% of those using aspirin, in 24.1% of those using LMWH, in 13.3% of those using DOACs, and in none of those using VKAs.

Conclusion We observed a high rate of VTE and bleeding events in our cohort. While the IMPEDE-VTE score predicted VTE risk, the SAVED score did not. No patient had a VTE while on oral anticoagulation. Patients who were not prescribed thromboprophylaxis had a high risk of both thrombosis and bleeding.

Publikationsverlauf

Artikel online veröffentlicht:
26. Februar 2024

• References

• 1 Carrier M, Le Gal G, Tay J, Wu C, Lee AY. 'Rates of venous thromboembolism in multiple myeloma patients undergoing immunomodulatory therapy with thalidomide or lenalidomide: a systematic review and meta-analysis.'. J Thromb Haemost 2011; 9 (04) 653-663
• 2 Farge D, Frere C, Connors JM, Khorana AA, Kakkar A, Ay C, Muñoz A, Brenner B, Prata PH, Brilhante D, Antic D, Casais P, Guillermo Esposito MC, Ikezoe T, Abutalib SA, Meillon-García LA, Bounameaux H, Pabinger I, Douketis J. '2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19.'. Lancet Oncol 2022; 23 (07) e334-e347
• 3 Li A, Wu Q, Luo S, Warnick GS, Zakai NA, Libby EN. et al. 'Derivation and Validation of a Risk Assessment Model for Immunomodulatory Drug-Associated Thrombosis Among Patients With Multiple Myeloma.'. J Natl Compr Canc Netw 2019; 17 (07) 840-7
• 4 Sanfilippo KM, Luo S, Wang TF, Fiala M, Schoen M, Wildes TM. et al. 'Predicting venous thromboembolism in multiple myeloma: development and validation of the IMPEDE VTE score.'. Am J Hematol 2019; 94 (11) 1176-84
• 5 Schulman S, Kearon C. 'Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients.'. J Thromb Haemost 2005; 3 (04) 692-4